P889: WILL OUTCOME IMPROVE BY TREATING MULTIPLE MYELOMA PATIENTS AT MRD RELAPSE? THE REMNANT STUDY (RELAPSE FROM MRD NEGATIVITY AS INDICATION FOR TREATMENT)
Authors: F. B. Askeland, A.-M. Rasmussen, A. Lysen, E. Haukås, A. Eilertsen, M. Moksnes, G. Tsykunova, A. Vik, B. D. Eiken, J. H. Sørbø, J. Rolke, K. O. Sand, R. F. Hallstensen, L. Myrseth, T. S. Slørdahl, F. Schjesvold
Journal: HemaSphere (2022)

Background: Although many new treatment modalities have become available, multiple myeloma (MM) is nevertheless considered an incurable disease. In recent years, the importance of achieving measurable residual disease (MRD) negativity is becoming more clearly defined in patients with MM. There is solid evidence that bone marrow MRD negativity is one of the strongest prognostic factors, and deeper responses correlate with increasingly favorable outcomes. The deepest and most durable responses are achieved in the first line (1.L) of treatment. Aims: The REMNANT study will evaluate if treating MRD relapse after 1.L therapy prolongs progression free survival (PFS) and overall survival (OS) compared to starting treatment at biochemical relapse/progressive disease (PD) in MM patients. Methods: The REMNANT study is an academic, multicenter, open-label, randomized phase II/III study of newly diagnosed (ND) MM patients eligible for autologous stem cell transplant (ASCT). Few exclusion criteria apply and patients with kidney failure and amyloidosis can be enrolled. 391 NDMM patients (age 18-75 years) eligible for ASCT will be enrolled in the phase II part of the study and receive standard of care (SOC) 1.L treatment according to Norwegian national guidelines; four pre-transplant induction and four post-transplant consolidation cycles of bortezomib, lenalidomide and dexamethasone (VRd). After induction, patients will undergo tandem or single transplant, depending on toxicity and response to first transplant. Following 1.L treatment 176 patients who are ≥ complete response (CR) and MRD negative (NGF Euroflow) will be enrolled in part 2 of the study. Patients will be randomized in a 1:1 ratio to receive second line treatment at MRD relapse in arm A or at PD in arm B. Randomization will be stratified by R-ISS stage at diagnosis and single versus tandem transplant. At loss of MRD negativity in arm A or at PD in arm B, second line treatment will be carfilzomib, dexamethasone and daratumumab until progressive disease. In part 2 we will compare different methods for measuring MRD; NGF Euroflow, Next Generation Sequencing (NGS), mass spectrometry and PET-CT. We will evaluate how the different methods compare when it comes to sensitivity and how they correlate to outcome (PFS and OS). The microbiota composition has shown to impact outcome in myeloma patients. Therefore, we will investigate how the microbiota at diagnosis differs in patients who achieve MRD negativity and those who still are MRD positive after treatment. Results: We will present updated results from part 1 of the study. As of February 16th 2022, 136 patients have been enrolled in part 1. Twenty-six patients have been evaluated for MRD status post consolidation. Thirteen patients (50%) were ≥CR and MRD negative and have been enrolled in part 2 of the study. In Table 1 baseline characteristics and results are presented. Image:Summary/Conclusion: Part 1 of the REMNANT study will clarify the overall response rate and depth of response measured by MRD, after SOC Norwegian 1.L treatment Part 2 will determine if treating patients at MRD relapse, when tumor burden is lower, will improve outcome.